ScienceDaily (Apr. 14, 2009) — The new science of epigenetics explains how genes can be modified by the environment, and a prime result of epigenetic inquiry has just been published online in The FASEB Journal: You are what your mother did not eat during pregnancy. In the research report, scientists from the University of Utah show that rat fetuses receiving poor nutrition in the womb become genetically primed to be born into an environment lacking proper nutrition.
As a result of this genetic adaptation, the rats were likely to grow to smaller sizes than their normal counterparts. At the same time, they were also at higher risk for a host of health problems throughout their lives, such as diabetes, growth retardation, cardiovascular disease, obesity, and neurodevelopmental delays, among others. Although the study involved rats, the genes and cellular mechanisms involved are the same as those in humans.
"Our study emphasizes that maternal–fetal health influences multiple healthcare issues across generations," said Robert Lane, professor of pediatric neonatology at the University of Utah, and one of the senior researchers involved in the study. "To reduce adult diseases such as diabetes, obesity, and cardiovascular disease, we need to understand how the maternal–fetal environment influences the health of offspring."
The scientists made this discovery through experiments involving two groups of rats. The first group was normal. The second group had the delivery of nutrients from their mothers' placentas restricted in a way that is equivalent to preeclampsia. The rats were examined right after birth and again at 21 days (21 days is essentially a preadolescent rat) to measure the amount of a protein, called IGF-1, that promotes normal development and growth in rats and humans. They found that the lack of nutrients caused the gene responsible for IGF-1 to significantly reduce the amount of IGF-1 produced in the body before and after birth.
"The new 'epigenetics' has taught us how nature is changed by nurture," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The jury's in and, yes, expectant moms really are eating for two. This study shows not only that we need to address problems such as preeclampsia during pregnancy, but also that prenatal care is far more important than anyone could have imagined a decade ago."
Please post a one paragraph response to this article. Expand on your thoughts and relate this information to content learned in class.
Wednesday, December 9, 2009
Monday, November 9, 2009
Keeping Chromosomes From Cuddling Up!
ScienceDaily (Dec. 3, 2008) — If chromosomes snuggle up too closely at the wrong times, the results can be genetic disaster.
Now researchers have found the molecular machines in fruit flies that yank chromosomes, the DNA-carrying structures, apart when necessary.
The machines, proteins called condensin II, separate chromosomes by twisting them into supercoils that kink up and therefore can no longer touch.
Scientists had known of condensin II but did not know how it functioned inside cells.
Keeping specific parts of chromosomes from touching can change how the instructions carried in the DNA are read, said research team leader Giovanni Bosco of The University of Arizona in Tucson.
"It's like picking up your favorite book and, depending on what chair you chose to sit in, it turned into a different story -- even though the printed words in the book never changed," Bosco, a UA assistant professor of molecular and cellular biology, wrote in an e-mail.
"This now changes the way we think about genetic information. Taking a literal reading of it is not what actually happens," he wrote. "Instead, context matters."
The team also found that condensin II plays a key role in making sure that fruit fly sperm cells each receive the proper number of chromosomes -- not too many, not too few.
Bosco suspects that condensin II plays the same role in the formation of human sperm and eggs.
Having too many or too few chromosomes in egg or sperm cells is the source of several important genetic disorders, including Down syndrome.
Abnormalities in chromosome number is also the cause of some miscarriages of early-term fetuses in humans.
The National Institutes of Health and the National Science Foundation funded the research.
Learning how cells control chromosomes and how DNA is transcribed will lead to better understanding of how an organism's DNA affects the organism's final form.
Scientists have known for about 50 years that when chromosomes are in direct contact, the transcription machinery can choose to transcribe either the gene from the mother or the gene from the father.
Many researchers investigated how the specific genes were brought close together so that process, known as transvection, could happen.
Bosco wondered, what if the chromosomes stayed stuck together?
To find something that separated chromosomes, he looked for female fruit flies that were sterile because chromosomes in their eggs had stuck together.
Once he had those fruit flies, Hartl isolated the gene that kept the chromosomes from coming apart. He found that the gene coded for condensin II, indicating that the sterile flies couldn't make condensin II.
To be able to watch how condensin II affects chromosomes, the researchers used the salivary glands from normal Drosophila melanogaster fruit flies. Fruit fly salivary glands are unusual, because they have many copies of the same chromosome coiled together like a rope.
Hartl said, "You can actually see chromosomes, because the cells are so huge and the chromosomes are so huge."
The team inserted an additional gene into the chromosomes that would turn the condensin II-producing gene off at 77 F (21 C) and on at 95 F (35 C). The researchers also marked one gene on the chromosomes with green fluorescent protein, or GFP, to be able to see changes in the chromosomes' positions.
The scientists then looked at the salivary glands at the two temperatures to see what happened when condensin II was present and when it was absent.
Bosco said, "Simply turning the condensin gene on or off, we could watch the chromosomes move right before our eyes, demonstrating that condensin was mostly likely the tiny machine that was ripping the chromosomes apart."
He said these findings are significant because more and more genetic tests to sequence people's DNA are becoming available, but the DNA sequence alone does not completely determine what diseases the person will have.
Even if it's in the genes, it might not show, he said. "It's what your cells are doing with your genes that's important."
To pull the chromosomes apart, condensin II changes its shape. Smith said the team's next step is figuring out how condensin II proteins are recruited to the chromosomes and how the condensin II proteins use the cellular energy packets known as ATP to change shape.
Journal references:
Hartl et al. Chromosome Alignment and Transvection Are Antagonized by Condensin II. Science, 2008; 322 (5906): 1384 DOI: 10.1126/science.1164216
Hartl et al. Condensin II Resolves Chromosomal Associations to Enable Anaphase I Segregation in Drosophila Male Meiosis. PLoS Genetics, 2008; 4 (10): e1000228 DOI: 10.1371/journal.pgen.1000228
Adapted from materials provided by University of Arizona, via EurekAlert!, a service of AAAS.
PLEASE POST A ONE PARAGRAPH RESPONSE TO THIS ARTICLE AND HOW IT RELATES TO YOU AND THE SUBJECT MATTER FROM CLASS!
Now researchers have found the molecular machines in fruit flies that yank chromosomes, the DNA-carrying structures, apart when necessary.
The machines, proteins called condensin II, separate chromosomes by twisting them into supercoils that kink up and therefore can no longer touch.
Scientists had known of condensin II but did not know how it functioned inside cells.
Keeping specific parts of chromosomes from touching can change how the instructions carried in the DNA are read, said research team leader Giovanni Bosco of The University of Arizona in Tucson.
"It's like picking up your favorite book and, depending on what chair you chose to sit in, it turned into a different story -- even though the printed words in the book never changed," Bosco, a UA assistant professor of molecular and cellular biology, wrote in an e-mail.
"This now changes the way we think about genetic information. Taking a literal reading of it is not what actually happens," he wrote. "Instead, context matters."
The team also found that condensin II plays a key role in making sure that fruit fly sperm cells each receive the proper number of chromosomes -- not too many, not too few.
Bosco suspects that condensin II plays the same role in the formation of human sperm and eggs.
Having too many or too few chromosomes in egg or sperm cells is the source of several important genetic disorders, including Down syndrome.
Abnormalities in chromosome number is also the cause of some miscarriages of early-term fetuses in humans.
The National Institutes of Health and the National Science Foundation funded the research.
Learning how cells control chromosomes and how DNA is transcribed will lead to better understanding of how an organism's DNA affects the organism's final form.
Scientists have known for about 50 years that when chromosomes are in direct contact, the transcription machinery can choose to transcribe either the gene from the mother or the gene from the father.
Many researchers investigated how the specific genes were brought close together so that process, known as transvection, could happen.
Bosco wondered, what if the chromosomes stayed stuck together?
To find something that separated chromosomes, he looked for female fruit flies that were sterile because chromosomes in their eggs had stuck together.
Once he had those fruit flies, Hartl isolated the gene that kept the chromosomes from coming apart. He found that the gene coded for condensin II, indicating that the sterile flies couldn't make condensin II.
To be able to watch how condensin II affects chromosomes, the researchers used the salivary glands from normal Drosophila melanogaster fruit flies. Fruit fly salivary glands are unusual, because they have many copies of the same chromosome coiled together like a rope.
Hartl said, "You can actually see chromosomes, because the cells are so huge and the chromosomes are so huge."
The team inserted an additional gene into the chromosomes that would turn the condensin II-producing gene off at 77 F (21 C) and on at 95 F (35 C). The researchers also marked one gene on the chromosomes with green fluorescent protein, or GFP, to be able to see changes in the chromosomes' positions.
The scientists then looked at the salivary glands at the two temperatures to see what happened when condensin II was present and when it was absent.
Bosco said, "Simply turning the condensin gene on or off, we could watch the chromosomes move right before our eyes, demonstrating that condensin was mostly likely the tiny machine that was ripping the chromosomes apart."
He said these findings are significant because more and more genetic tests to sequence people's DNA are becoming available, but the DNA sequence alone does not completely determine what diseases the person will have.
Even if it's in the genes, it might not show, he said. "It's what your cells are doing with your genes that's important."
To pull the chromosomes apart, condensin II changes its shape. Smith said the team's next step is figuring out how condensin II proteins are recruited to the chromosomes and how the condensin II proteins use the cellular energy packets known as ATP to change shape.
Journal references:
Hartl et al. Chromosome Alignment and Transvection Are Antagonized by Condensin II. Science, 2008; 322 (5906): 1384 DOI: 10.1126/science.1164216
Hartl et al. Condensin II Resolves Chromosomal Associations to Enable Anaphase I Segregation in Drosophila Male Meiosis. PLoS Genetics, 2008; 4 (10): e1000228 DOI: 10.1371/journal.pgen.1000228
Adapted from materials provided by University of Arizona, via EurekAlert!, a service of AAAS.
PLEASE POST A ONE PARAGRAPH RESPONSE TO THIS ARTICLE AND HOW IT RELATES TO YOU AND THE SUBJECT MATTER FROM CLASS!
Monday, November 2, 2009
Alcoholism & Genetics!!!
A Person's High Or Low Response To Alcohol Says Much About Their Risk For Alcoholism
ScienceDaily (May 25, 2009) — Someone who has a low level of response (LR) to alcohol, meaning relatively little reaction to alcohol, has a higher risk for developing alcohol-use disorders (AUDs). A study that examined the influence of LR in conjunction with other characteristics – like family history of AUDs and age of drinking onset – has found that LR is a unique risk factor for AUDs across adulthood and is not simply a reflection of a broader range of risk factors.
"If a person needs more alcohol to get a certain effect, that person tends to drink more each time they imbibe," explained Marc A. Schuckit, director of the Alcohol Research Center, Veterans Affairs San Diego Healthcare System, professor of psychiatry at the University of California, San Diego, and corresponding author for the study.
"Other studies we have published have shown that these individuals also choose heavy drinking peers, which helps them believe that what they drink and what they expect to happen in a drinking evening are 'normal,'" he said. "This low LR, which is perhaps a low sensitivity to alcohol, is genetically influenced."
Schuckit and his colleagues examined 297 men participating in the San Diego Prospective Study, originally recruited and tested on their level of reaction to alcohol when they were 18 to 25 years old. Each reported on family history of AUDs, typical drinking quantity, age of drinking onset, body mass index, and initial age at recruitment for the study. AUDs were evaluated at 10-, 15-, 20-, and 25-year follow-ups.
Results showed that a low LR to alcohol predicted AUD occurrence over the course of adulthood even after controlling for the effects of other robust risk factors. In short, LR is a unique risk factor for AUDs across adulthood, and not simply a reflection of a broader range of risk factors.
"A low LR at age 20 was not just a reflection of being a heavier drinker at age 20 when we tested these men, and it wasn't an artifact of an earlier onset of drinking," said Schuckit. "We showed that a low LR at 20 predicts later heavy drinking and alcoholism even if you control for all these other predictors of alcohol problems at age 20."
Schuckit added that the study's method of examination – establishing multiple predictors at age 20, revisiting participants about every five years, and securing a response rate of about 94 percent – strongly show that LR is consistent and powerful in predicting alcoholism."
"Because alcoholism is genetically influenced, and because a low LR is one of the factors that adds to the risk of developing alcoholism," said Schuckit, "if you're an alcoholic, you need to tell your kids they are at a four-fold increased risk for alcoholism. If your kid does drink, find out if they can 'drink others under the table,' and warn them that that is a major indication they have the risk themselves. Keep in mind, however, that the absence of a low LR doesn't guarantee they won't develop alcoholism, as there are other risk factors as well."
It's not all bad news, Schuckit added. "We are looking for ways to identify this risk early in life, and to find ways to decrease the risk even if you carry a low LR … so there is hope for the future."
--------------------------------------------------------------------------------
Journal reference:
. The Relationships of the Level of Response to Alcohol and Additional Characteristics to Alcohol Use Disorders across Adulthood: A Discrete-Time Survival Analysis. Alcoholism: Clinical & Experimental Research, In Print September 2009
DIRECTIONS-PLEASE POST A ONE PARAGRAPH RESPONSE TO THIS ARTICLE BY SUNDAY, NOV. 8, 2009, 10PM.
ScienceDaily (May 25, 2009) — Someone who has a low level of response (LR) to alcohol, meaning relatively little reaction to alcohol, has a higher risk for developing alcohol-use disorders (AUDs). A study that examined the influence of LR in conjunction with other characteristics – like family history of AUDs and age of drinking onset – has found that LR is a unique risk factor for AUDs across adulthood and is not simply a reflection of a broader range of risk factors.
"If a person needs more alcohol to get a certain effect, that person tends to drink more each time they imbibe," explained Marc A. Schuckit, director of the Alcohol Research Center, Veterans Affairs San Diego Healthcare System, professor of psychiatry at the University of California, San Diego, and corresponding author for the study.
"Other studies we have published have shown that these individuals also choose heavy drinking peers, which helps them believe that what they drink and what they expect to happen in a drinking evening are 'normal,'" he said. "This low LR, which is perhaps a low sensitivity to alcohol, is genetically influenced."
Schuckit and his colleagues examined 297 men participating in the San Diego Prospective Study, originally recruited and tested on their level of reaction to alcohol when they were 18 to 25 years old. Each reported on family history of AUDs, typical drinking quantity, age of drinking onset, body mass index, and initial age at recruitment for the study. AUDs were evaluated at 10-, 15-, 20-, and 25-year follow-ups.
Results showed that a low LR to alcohol predicted AUD occurrence over the course of adulthood even after controlling for the effects of other robust risk factors. In short, LR is a unique risk factor for AUDs across adulthood, and not simply a reflection of a broader range of risk factors.
"A low LR at age 20 was not just a reflection of being a heavier drinker at age 20 when we tested these men, and it wasn't an artifact of an earlier onset of drinking," said Schuckit. "We showed that a low LR at 20 predicts later heavy drinking and alcoholism even if you control for all these other predictors of alcohol problems at age 20."
Schuckit added that the study's method of examination – establishing multiple predictors at age 20, revisiting participants about every five years, and securing a response rate of about 94 percent – strongly show that LR is consistent and powerful in predicting alcoholism."
"Because alcoholism is genetically influenced, and because a low LR is one of the factors that adds to the risk of developing alcoholism," said Schuckit, "if you're an alcoholic, you need to tell your kids they are at a four-fold increased risk for alcoholism. If your kid does drink, find out if they can 'drink others under the table,' and warn them that that is a major indication they have the risk themselves. Keep in mind, however, that the absence of a low LR doesn't guarantee they won't develop alcoholism, as there are other risk factors as well."
It's not all bad news, Schuckit added. "We are looking for ways to identify this risk early in life, and to find ways to decrease the risk even if you carry a low LR … so there is hope for the future."
--------------------------------------------------------------------------------
Journal reference:
. The Relationships of the Level of Response to Alcohol and Additional Characteristics to Alcohol Use Disorders across Adulthood: A Discrete-Time Survival Analysis. Alcoholism: Clinical & Experimental Research, In Print September 2009
DIRECTIONS-PLEASE POST A ONE PARAGRAPH RESPONSE TO THIS ARTICLE BY SUNDAY, NOV. 8, 2009, 10PM.
Monday, October 5, 2009
Sequencing Thousand And One Genomes
Researchers report the simultaneous completion of the first genomes of wild Arabidopsis thaliana strains as part of the 1001 Genomes Project.
Researchers at the Max Planck Institute for Developmental Biology in Tuebingen, Germany, reported the completion of the first genomes of wild strains of the flowering plant Arabidopsis thaliana. The entire genomes of two individuals of this species, one from Ireland, the other from Japan, have now been compared in great detail. They were found to be astonishingly different from each other, as Detlef Weigel and his colleagues write in Genome Research.
This study marks the starting point of the 1001 Genomes Project in which a total of thousand and one individuals of the same species will be sequenced. The scientists aim at correlating the genetic differences between the different strains with variation in the speed of plant growth and their resistance against infectious germs. These strategies could then also be applied to crop plants or trees.
Every genome is different. Everybody knows that the genome of apes must be different from our human genome and that both are different from the genome of a sunflower. It is only a few years ago that a huge research community produced at great cost a single human genome sequence. The assumption was that it would unlock all the essential features of our species, since any differences between us were thought to be very minor, on the order of 0.1 percent of the entire genome.
Similar views prevailed for other species, including thale cress Arabidopsis thaliana, a model organism in plant science. It is one of the best-understood organisms on earth, however, the genetic differences that allow different strains of this plant to thrive in very different places all over the Northern hemisphere are largely unknown.
Until very recently, it was assumed that the similarity in appearance of different individuals of thale cress is matched by a similar degree of similarity in the genetic material. “But is it really true that such subtle differences in our DNA or in that of thale cress can account for the great variation in individual traits? Is there indeed something like ‘the’ genome of a species, or do have to change our point of view and focus on the genome of an individual?” asks Detlef Weigel, director at the Max Planck Institute for Development Biology.
Recent advances in the technology of DNA sequencing have reduced the price for reading a single genome by several orders of magnitude, and this can now be accomplished within a week, rather than months or years. However, there are still few analytical tools for the torrent of data produced by the new generation of sequencing machines, such as the one sold by the San Diego based company Illumina. The Max Planck Institute group had to overcome a series of technical challenges to reconstruct the genome sequences of the two strains it analyzed from the rather short snippets of sequences that the Illumina instrument delivers. But the first feasibility study has now been finished, demonstrating that even with these very short sequence reads not only point differences can be identified, but also missing or extra genetic material can be tracked down. “We are confident that our method is robust, and we have begun to sequence the genomes of 80 thale cress strains”, says Weigel. The project should be finished by January 2009.
The study marks the start of a project on a much larger scale. Within the next two years the 1001 Genomes project, spearheaded by Weigel, plans to sequence at least 1001 different thale cress individuals from around the world. The hope is that armed with this information, it will be possible to correlate genetic differences with variation in the speed with which plants grow, how much they branch, or how well they resist infectious germs. This project, in turn, will inform similar projects on crop plants, which have much larger genomes and are therefore more difficult to analyze.
While this is very exciting, the task will not be done once every individual genome is sequenced. In every cell, the genomes are packaged in different ways, allowing for different activities of the same genetic material. With the next sequencing techniques, these subtle differences can be studied as well. Thus, the 1001 Genomes project will peel away only the first layer of variation.
--------------------------------------------------------------------------------
Journal reference:
Ossowski et al. Sequencing of natural strains of Arabidopsis thaliana with short reads. Genome Research, September 25, 2008; DOI: 10.1101/gr.080200.108
Please respond with a paragraph response addressing your thoughts, implications on society, where this project is at right now (this requires additional research), etc. (10 points)
Researchers at the Max Planck Institute for Developmental Biology in Tuebingen, Germany, reported the completion of the first genomes of wild strains of the flowering plant Arabidopsis thaliana. The entire genomes of two individuals of this species, one from Ireland, the other from Japan, have now been compared in great detail. They were found to be astonishingly different from each other, as Detlef Weigel and his colleagues write in Genome Research.
This study marks the starting point of the 1001 Genomes Project in which a total of thousand and one individuals of the same species will be sequenced. The scientists aim at correlating the genetic differences between the different strains with variation in the speed of plant growth and their resistance against infectious germs. These strategies could then also be applied to crop plants or trees.
Every genome is different. Everybody knows that the genome of apes must be different from our human genome and that both are different from the genome of a sunflower. It is only a few years ago that a huge research community produced at great cost a single human genome sequence. The assumption was that it would unlock all the essential features of our species, since any differences between us were thought to be very minor, on the order of 0.1 percent of the entire genome.
Similar views prevailed for other species, including thale cress Arabidopsis thaliana, a model organism in plant science. It is one of the best-understood organisms on earth, however, the genetic differences that allow different strains of this plant to thrive in very different places all over the Northern hemisphere are largely unknown.
Until very recently, it was assumed that the similarity in appearance of different individuals of thale cress is matched by a similar degree of similarity in the genetic material. “But is it really true that such subtle differences in our DNA or in that of thale cress can account for the great variation in individual traits? Is there indeed something like ‘the’ genome of a species, or do have to change our point of view and focus on the genome of an individual?” asks Detlef Weigel, director at the Max Planck Institute for Development Biology.
Recent advances in the technology of DNA sequencing have reduced the price for reading a single genome by several orders of magnitude, and this can now be accomplished within a week, rather than months or years. However, there are still few analytical tools for the torrent of data produced by the new generation of sequencing machines, such as the one sold by the San Diego based company Illumina. The Max Planck Institute group had to overcome a series of technical challenges to reconstruct the genome sequences of the two strains it analyzed from the rather short snippets of sequences that the Illumina instrument delivers. But the first feasibility study has now been finished, demonstrating that even with these very short sequence reads not only point differences can be identified, but also missing or extra genetic material can be tracked down. “We are confident that our method is robust, and we have begun to sequence the genomes of 80 thale cress strains”, says Weigel. The project should be finished by January 2009.
The study marks the start of a project on a much larger scale. Within the next two years the 1001 Genomes project, spearheaded by Weigel, plans to sequence at least 1001 different thale cress individuals from around the world. The hope is that armed with this information, it will be possible to correlate genetic differences with variation in the speed with which plants grow, how much they branch, or how well they resist infectious germs. This project, in turn, will inform similar projects on crop plants, which have much larger genomes and are therefore more difficult to analyze.
While this is very exciting, the task will not be done once every individual genome is sequenced. In every cell, the genomes are packaged in different ways, allowing for different activities of the same genetic material. With the next sequencing techniques, these subtle differences can be studied as well. Thus, the 1001 Genomes project will peel away only the first layer of variation.
--------------------------------------------------------------------------------
Journal reference:
Ossowski et al. Sequencing of natural strains of Arabidopsis thaliana with short reads. Genome Research, September 25, 2008; DOI: 10.1101/gr.080200.108
Please respond with a paragraph response addressing your thoughts, implications on society, where this project is at right now (this requires additional research), etc. (10 points)
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